Cms/files/59829/1534427532A Systematic Review of Medicinal Plants Used For Weight Loss in Brazil

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Author’s Accepted Manuscript

A systematic review of medicinal plants used for


weight loss in Brazil: Is there potential for obesity
treatment?

Luana M. Cercato, Pollyanna A.S. White,


Fernando K. Nampo, Márcio R.V. Santos, Enilton
A. Camargo
www.elsevier.com/locate/jep

PII: S0378-8741(15)30197-5
DOI: http://dx.doi.org/10.1016/j.jep.2015.10.038
Reference: JEP9795
To appear in: Journal of Ethnopharmacology
Received date: 23 May 2015
Revised date: 24 October 2015
Accepted date: 26 October 2015
Cite this article as: Luana M. Cercato, Pollyanna A.S. White, Fernando K.
Nampo, Márcio R.V. Santos and Enilton A. Camargo, A systematic review of
medicinal plants used for weight loss in Brazil: Is there potential for obesity
t r e a t m e n t ? , Journal of Ethnopharmacology,
http://dx.doi.org/10.1016/j.jep.2015.10.038
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A systematic review of medicinal plants used for weight loss in Brazil: is there
potential for obesity treatment?

Luana M. Cercato1, Pollyanna A. S. White¹, Fernando K. Nampo1, Márcio R. V.


Santos1, Enilton A. Camargo1#

1
Department of Physiology, Federal University of Sergipe, (UFS), São Cristóvão,
49100-000, SE, Brazil

Review Article

#Corresponding author: Enilton A Camargo; PhD; Department of Physiology, Federal


University of Sergipe (UFS), São Cristóvão, 49100-000, SE, Brazil; Telephone number:
+55-79-2105-6644; E-mail: [email protected]

1
Graphical abstract

Systematic review of Plants most cited:


ethnobotanical surveys in Brazil
1º Bacharis trimera (Less.) DC.

No study or little
scientific
2º Annona muricata L. evidence
corroborating
the traditional use
Plants popularly used for weight loss
for weight loss: 3º Hancornia speciosa Gomes
50 plant species cited by
population

2
Abstract

Ethnopharmacological relevance: Obesity is a pandemic disease and its prevalence is


still increasing. Moreover, it has important costs to public health. In Brazil, many plants
are used for weight loss by overweight or obese people, but there is a lack of scientific
basis for this practice. Many ethnobotanical studies aiming to characterize this usage
have been published, but they are still limited by the region considered and the diversity
of the popular knowledge. Aim of the study: The present study was undertaken to
systematically review the ethnobotanical surveys regarding the species utilized to
reduce body weight in overweight or obese people in Brazil. Methods: Ethnobotanical
surveys related to this usage and performed in Brazilian regions were systematically
found in MEDLINE, LILACS and Scopus. Results: Thirty-three studies were included
in this review. Forty-eight species were popularly utilized to lose weight. The most cited
species were Baccharis trimera (Less.) DC, Annona muricata L. and Hancornia
speciosa Gomes. Camellia sinensis (L.) Kuntze and Hibiscus sabdariffa L. were also
cited and are supported by either animal or human investigations that indicate some
beneficial activity against obesity. However, for the majority of species cited in the
included studies, there is no scientific basis that assures the biological effects of this
usage. Many studies have demonstrated important effects of these plants on glycemia,
serum lipid levels or body weight control in non-obese conditions, which is not
sufficient to recommend the use of these plants to reduce body weight in overweight or
obese people. Conclusions: Although many plants are popularly used to reduce weight
in overweight or obese people in Brazil, there is little scientific evidence corroborating
its usage. Based on the ethnobotanical data presented, this review indicates the plants
that should be considered for scientifically controlled studies devoted to investigating
their effects on obesity.

Keywords: Ethnobotanical survey, Obesity, Weight loss, Medicinal plants, Brazil.

3
1. Introduction

Obesity is a worldwide disease that affects 27.5% of adults and 47.1% of


children. The number of obese and overweight people has increased from 587 million in
1980 to 2.1 billion in 2013, with one of the highest costs to public health. In addition,
obesity is associated with physical restrictions and a higher mortality rate, not only due
to obesity itself but also due to comorbidities such as metabolic syndrome, diabetes,
osteoarthritis and cancer. Obesity control has been ineffective, and 3.4 million deaths
around the world were attributed to obesity in 2010 (Ng et al., 2014).
The Brazilian Survey on Family Budgets (Pesquisa de Orçamentos Familiares -
POF) in 2008-2009 indicated that obesity and overweight have increased in prevalence
in all age groups. According to this research, 50% of men and 48% of women were
overweight and 12.5% of men and 16.9% of women were obese (Brasil, 2010).
The prevention and treatment of obesity include a healthy lifestyle with regular
physical exercise and balanced diet, accompanied in some cases by pharmacological
therapy and/or surgical procedures (McTigue et al., 2003). Currently, natural products
represent an increasingly popular option to help treat obesity because many are
considered efficient, safe and, in many cases, less expensive in comparison with drugs
conventionally used to treat obesity (Manenti, 2010). Some species were described for
the treatment of obesity, such as Camellia sinensis (L.) Kuntze (green tea; Grove and
Lambert, 2010; Huang et al., 2014), Citrus aurantium (L.) (bitter orange; Stohs et al.,
2012) and Phaseolus vulgaris L. (white bean, Barrett and Udani, 2011).
In Brazil, it was shown that more than 90% of the population has used a
medicinal plant, and it is estimated that the phytotherapy industry makes approximately
1 billion reais per year (Correa and Alves, 2008). Many ethnobotanical surveys have
described the traditional use of plants to lose weight (e.g., Dickel et al., 2007; Grandi et
al., 1989; Silva et al., 2010), but these are restricted to small areas of Brazil. Thus, there
is a lack of integrated data from ethnobotanical surveys from these delimited areas in
diverse parts of the country. A scientific survey of species popularly used to lose weight
can benefit both the health of the community and the potential development,
management, and commercialization of medicinal plants and their subproducts by the
food, phytotherapy and pharmaceutical industries to help treat obesity.

4
With this in mind, this study was undertaken to review the plant species
popularly used to reduce body weight in overweight or obese people in Brazil.

5
2. Methodology

2.1. Search strategy

Surveys were identified using electronic databases including MEDLINE (via


PubMed), Scopus and the Latin-American and Caribbean Center on Health Sciences
Information (LILACS). The following keywords were used: “ethnobotanical,”
“medicinal,” “plant,” “obesity,” “weight loss,” “Brazil” and their MeSH variations. The
search strategy was designed to include all articles containing the descriptors that were
published until February 27, 2015, with no end date limit. There was no restriction
regarding language for the identified articles.

2.2. Study selection and inclusion/exclusion criteria

All titles, abstracts and complete articles were independently reviewed by two
collaborators (LMC and PASW). The selected articles were required to have considered
the ethnobotanical application or use of any medicinal plants in obese or overweight
people.

2.3. Data extraction

The data were extracted by one collaborator (LMC) using a standardized form
and was verified for its quality and accuracy by a second collaborator (PASW). The
information extracted included the species and family of the plants, the traditional use,
the part of the plant used, the procedure of preparation, the region of the country where
the use was described and the route of administration.

6
3. Results and discussion

The database search yielded 467 records. After removing duplicates, 311
remained, of which 224 were excluded based on title and abstract. Eighty-seven full
texts were assessed, and 54 were excluded, as they did not meet the review criteria.
Thirty-three studies were included in the present review (Figure 1).
Fifty species used for body weight reduction were cited (Table 1). The states of
Brazil that presented higher ethnobotanical diversity were Mato Grosso (15 species),
Minas Gerais (13 species), Bahia, Pernambuco and Rio Grande do Sul (10 species),
Santa Catarina (7 species) and Mato Grosso do Sul (6 species).

The species (followed by popular name) that showed the highest number of
citations were Baccharis trimera (Less.) DC. ("carqueja" / "carqueja amarga") with 15
citations, Annona muricata Linn. ("graviola") with 6 citations and Hancornia speciosa
Gomes ("mangaba") with 4 citations. Other cited species are shown in Table 1. For most
plants cited, the decoction or infusion preparations of leaves or barks were mentioned,
but for some of the whole plants, the root or fruits were also cited. Furthermore, it was
noted that all the preparations of the plants were administered by an oral route. Table 1
shows that in many studies, the information concerning the method of preparation
and/or the part of the plant used was missing (e.g., Bieski et al., 2012 and Dickel et al.,
2007). This highlights the need for more detailed description of the results in the
ethnobotanical surveys to minimize the risk of bias of these studies.

Although our results raise the possibility that medicinal plants may present a
beneficial effect in the treatment of obesity, the prevalence of its usage is not sufficient
to declare its usefulness to treat obesity or cause weight loss. In fact, people use these
plants due to their ease of access, but they are far from serving as a therapeutic
intervention because the objective generally seems to be weight loss. However, if a
plant is effective in promoting weight loss (or even treat a comorbidity presented by
obese or overweight people), it may have potential for the treatment of obesity, which
needs to be confirmed. Therefore, we discuss the plants referenced in the included
studies in the present review.

7
LILACS Pubmed Scopus
(n=76) (n=184) (n=207)

467 records No additional records


identified through identified through
database searching other sources

311 records
after duplicates
removed

224 records
311 records
excluded on
screened
title and abstract

54 full-text articles
87 full-text articles excluded:
assessed for elegibility - did not meet
review criteria (n=54)

33 studies included
in qualitative synthesis

Figure 1: Study flow diagram.

8
Table 1: Plants cited by ethnobotanical studies in Brazilian regions for body weight loss or as anti-obesity agents.

Part of Number
Popular Preparation
Specie Family the Region of Brazil of Reference
name method
plant citations
Abarema cochliocarpos
Whole
(Gomes) Barneby & J.W. Leguminosae Barbatimão Decoction Salvador - BA 1 Cunha Lima et al. (2008)
plant
Grimes
Achyrocline satureioides Whole Dickel et al. (2007); Vendruscolo et al.
Compositae Macela Infusion Porto Alegre - RS 2
(Lam.) DC. plant (2005)
Decoction,
Allium sativum L. Amaryllidaceae Alho Fruit infusion or Assaré - CE 1 Macêdo et al. (2013)
licking
Anacardium occidentale L. Anacardiaceae Cajueiro Leaves Decoction *MG 1 Grandi et al. (1989)
Jaca-de-
Annona montana Macfad. Annonaceae Leaves Decoction Salvador - BA 1 Cunha Lima et al. (2008)
pobre
Cujubim – RO; *MG; dos Santos and de Lima (2008); Grandi
Decoction or Ituiutaba - MG; Assaré et al. (1989); Liporacci and Simão
Annona muricata L. Annonaceae Graviola Leaves 6
infusion – CE Vila Cachoeira – (2013); Macêdo et al. (2013); Moreira
BA; Queimadas - PB; et al. (2002); Santos et al. (2012)
Decoction,
Aspargo, Whole infusion or
Asparagus officinalis L. Asparagaceae *MG 1 Grandi et al. (1989)
milindre plant dyeing or
tincture

9
Vila Velha - ES;
Poconé - MT; Extrema
Albertasse et al. (2010); Bieski et al.
- MG; Recife – PE;
(2012); Costa and Mayworm (2011); de
Porto Alegre – RS;
Albuquerque et al. (2007); Dickel et al.
Cujubim – RO; *MG;
(2007); dos Santos and de Lima (2008);
Carqueja, São Gabriel – RS;
Baccharis trimera (Less.) Whole Grandi et al. (1989); Lobler et al.
Compositae carqueija Infusion Santa Cruz – RJ; 15
DC. plant (2014); Lopes and Pantoja (2013);
amarga Ascurra –SC;
Meyer et al. (2012); Moreira et al.
Cachoeira – BA;
(2002); Nunes et al. (2003); Rodrigues
Campo Grande - MS;
and Carvalho (2001); Ribeiro et al.
Alto Rio Grande - MG;
(2010); Zeni and Bosio (2011)
Vila Ingaí- MG; Nova
Rússia - SC
Unha-de- Whole *MG; Alto Rio Grande
Bauhinia rufa (Bong.) Decoction or Grandi et al. (1989); Rodrigues and
Leguminosae vaca, pata- plant or - MG; Nova Xavantina 3
Steud. infusion Carvalho (2001); Silva et al. (2010)
de-vaca leaves – MT
Carrapixo-
Bidens bipinnata L. Compositae Leaves Decoction Salvador - BA 1 Cunha Lima et al. (2008)
de-agulha
Byrsonima sericea DC. Malpighiaceae Murici Leaves Decoction Salvador - BA 1 Cunha Lima et al. (2008)
São José dos Cordeiros
Camellia sinensis (L.) Leite et al. (2013); Lobler et al. (2014);
Theaceae Chá-verde Leaves Infusion – PB; São Gabriel - RS 3
Kuntze Pinto et al. (2013)
Cuiabá- MT
Campomanesia Bark,
xanthocarpa (Mart.) Myrtaceae Guabiroba leaves NR Porto Alegre - RS 1 Dickel et al. (2007)
O.Berg or roots
Caryocar brasiliense
Caryocaraceae Pequizeiro NR NR Poconé - MT 1 Bieski et al. (2012)
A.St.-Hil.
Cinnamomum verum Canela-da-
Lauraceae NR Infusion Poconé - MT 1 Bieski et al. (2012)
J.Presl india
Limão,
Citrus limon (L.) Osbeck Rutaceae limão- Fruit Infusion Porto Alegre - RS 1 Vendruscolo et al. (2005)
bergamota

10
#
Clavija nutans (Vell.)
Primulaceae Porangaba NR NR Campo Grande - MS 1 Nunes et al. (2003)
B.Stahl
Xinxim-de- Whole Ilhéus – BA; Vila
Cleome aculeata L. Cleomaceae Infusion 2 Feijó et al. (2013); Moreira et al. (2002)
galinha plant Cachoeira – BA
Café,
Coffea arabica L. Rubiaceae Leaves Infusion *MG 1 Grandi et al. (1989)
cafeeiro
#
Cordia ecalyculata Vell. Boraginaceae Porangaba Leaves NR Santa Cruz - RJ 1 Lopes and Pantoja (2013)
Cana-
Cymbopogon citratus cidreira,
Poaceae Leaves Infusion Porto Alegre - RS 1 Vendruscolo et al. (2005)
(DC.) Stapf capim-
cidreira
Flowers Santa Cruz - RJ
Lopes and Pantoja (2013); Meyer et al.
Cynara scolymus L. Compositae Alcachofra or Infusion Ascurra - SC; Videira 3
(2012); Silva and Bündchen (2011)
leaves – SC
Echinodorus macrophyllus Chapéu-de- Campo Grande - MS;
Alismataceae Leaves Infusion 2 Nunes et al. (2003); Silva et al. (2010)
(Kunth) Micheli couro Nova Xavantina - MT
Emilia sonchifolia (L.)
Compositae Vassourinha Leaves Infusion Jupi- PE 1 Teixeira and Melo (2006)
DC. ex DC.
Erythrina dominguezii
Leguminosae Maleitoso NR NR Campo Grande - MS 1 Nunes et al. (2003)
Hassl.
chico-
Guazuma ulmifolia Lam. Malvaceae Bark Infusion Dourados - MS 1 Alves et al. (2008)
magro
Decoction, da Silva et al. (2010); Grandi et al.
Hancornia speciosa Caxias – MA; *MG;
Apocynaceae Mangaba Bark infusion or 4 (1989); Santos et al. (2013); Silva et al.
Gomes Nova Xavantina – MT
ointment (2010)

Hibiscus sabdariffa L. Malvaceae Hibiscus Flowers NR Porto Alegre - RS 1 Dickel et al. (2007)

Leaves
#
Luehea divaricata Mart. Malvaceae Porangaba and NR Porto Alegre - RS 1 Dickel et al. (2007)
bark

11
Dorme- Decoction or
Mimosa pudica L. Leguminosae Leaves Ascurra- SC 1 Meyer et al. (2012)
Dorme infusion
Oxalis hirsutissima Mart.
Oxalidaceae Azedinha NR Infusion Poconé – MT 1 Bieski et al. (2012)
ex Zucc.
Nova Xavantina – MT;
Palicourea coriacea Silva et al. (2010); Souza and Felfili
Rubiaceae Douradinha Leaves Infusion Alto Paraíso de Goiás 3
(Cham.) K. Schum (2006); Souza et al. (2013)
– GO
Pfaffia glomerata Ginseng-
Amaranthaceae NR Infusion Poconé – MT 1 Bieski et al. (2012)
(Spreng.) Pedersen brasileiro
Leaves
Piper mikanianum (Kunth)
Piperaceae Coroninha and NR Porto Alegre - RS 1 Dickel et al. (2007)
Steud.
roots
Infusion or
Rubus brasiliensis Mart. Rosaceae Amoreira NR dyeing or Poconé – MT 1 Bieski et al. (2012)
tincture
Rudgea viburnoides Congonha- Leaves
Rubiaceae NR Campo Grande - MS 2 Nunes et al. (2003); Souza et al. (2013)
(Cham.) Benth. de-bugre or root
Scutia buxifolia Reissek Rhamnaceae Coronilha Bark NR Porto Alegre - RS 1 Dickel et al. (2007)
Recife – PE; Porto
Senna occidentalis (L.) de Albuquerque et al. (2007); Dickel et
Leguminosae Manjerioba Leaves Infusion Alegre – RS; 3
Link al. (2007); Fuck et al. (2005)
Bandeirantes – PR
Sida rhombifolia L. Malvaceae Guaxuma NR Infusion Poconé – MT 1 Bieski et al. (2012)
Simaba ferruginea A. St.-
Simaroubaceae Calunga NR Maceration Poconé – MT 1 Bieski et al. (2012)
Hil.
Panaceia,
Leaves Santa Teresa – ES; Gallotte and Ribeiro (2005); Lopes and
Solanum cernuum Vell. Solanaceae pata de NR 2
or root Santa Cruz - RJ Pantoja (2013)
mono
Spondias mombim L. Anacardiaceae Cajá Leaves Juice Vila Velha - ES 1 Albertasse et al. (2010)
Stevia rebaudiana
Compositae Estévia NR NR Santa Teresa - ES 1 Gallotte and Ribeiro (2005)
(Bertoni) Bertoni
Syagrus romanzoffiana
Arecaceae Coqueiro Leaves NR Nova Rússia - SC 1 Zeni and Bosio (2011)
(Cham.) Glassman

12
Poconé – MT; Nova Bieski et al. (2012); Zeni and Bosio
Symphytum officinale L. Boraginaceae Confrei Leaves Infusion 2
Rússia - SC; (2011)
Syzygium cumini (L.) Salvador – BA; Porto Cunha Lima et al. (2008); Dickel et al.
Myrtaceae Jamelão Leaves Decoction 2
Skeels Alegre – RS; (2007)
Catinga-de-
Tanacetum vulgare L. Compositae Leaves NR Porto Alegre- RS 1 Dickel et al. (2007)
mulata
Terminalia catappa L. Combretaceae Castanhola Leaves Infusion Queimadas - PB 1 Santos et al. (2012)
Recife - PE; Ituiutaba
Vernonia condensata de Albuquerque et al. (2007); Liporacci
Compositae Boldo Leaves Infusion – MG; Queimadas – 3
Baker and Simão (2013); Santos et al. (2012)
PB
Decoction or
Vochysia rufa Mart. Vochysiaceae Pau-doce NR Poconé – MT 1 Bieski et al. (2012)
Infusion
NR (not referenced) indicates the lack of the specific information in the reference. States of Brazil: Bahia (BA); Ceará (CE), Espírito Santo (ES),
Maranhão (MA), Mato Grosso (MT), Mato Grosso do Sul (MS), Minas Gerais (MG), Paraíba (PB), Paraná (PR), Pernambuco (PE), Rio de
Janeiro (RJ), Rio Grande do Sul (RS), Rondônia (RO), Santa Catarina (SC). * City not specified, the whole State of MG was considered. #
Species that were referred to by the same popular name but were identified by different scientific names in the references.

13
3.1. Baccharis trimera (Less.) DC.

Baccharis trimera (Less.) DC. (Compositae) is traditionally known as


“carqueja” and is found in tropical regions. All parts of the plant are widely used in
traditional medicine as an infusion for body weight loss in various Brazilian states (de
Souza et al., 2012). Additionally, this plant is popularly used for relieving climacteric
symptoms, hypertension, anemia, fever, rheumatism, urinary infection, gallstones,
diabetes, hepatic obstruction, helminthic infection and scalp diseases (Albertasse et al.,
2010; Albuquerque, 1997; Bieski et al., 2012; Costa and Mayworm, 2011; dos Santos
and de Lima, 2008; Grandi et al., 1989; Lopes and Pantoja, 2013; Meyer et al., 2012;
Moreira et al., 2002; Nunes et al., 2003; Rodrigues and Carvalho, 2001; Zeni and Bosio,
2011).
In addition to being the species with the highest number of citations for popular
use in our review, B. trimera was also found to have a higher diversity of
pharmacological actions compared to the other plants evaluated. Studies have shown
that B. trimera possesses antimicrobial (Avancini et al., 2000; Fabri et al., 2011),
antiulcer (Biondo et al., 2011; Dias et al., 2009), anti-inflammatory and analgesic
activities (Gene et al., 1996). Additionally, Oliveira et al. (2005) showed a
hypoglycemic effect in diabetic mice treated for seven days with 2 g/kg of the aqueous
fraction of B. trimera.
The methanol extract of B. trimera causes inhibition in vitro of both pancreatic
lipase, an enzyme that hydrolyses triglycerides, and α and β-glucosidases, which
catalyze the hydrolysis of glucosidic bounds, generating glucose (Souza et al., 2011).
Moreover, Assaid et al. (2012) described the inhibition of α-glycosidase but not lipase
by the aqueous extract of B. trimera. Some studies have described that lipase inhibitors
were isolated in the alcoholic extracts of plants, particularly methanol extracts, and
suggested that organic compounds soluble in methanol might present some structural
characteristics that favor the binding and inhibition of lipase (Sharma et al., 2005;
Sugimoto et al., 2009). It seems that the differences in the solvent used to prepare the
extracts, methanol in the former and aqueous in the latter study, may account for the
discrepancies regarding lipase inhibition (Assaid et al., 2012; Souza et al., 2011). In
spite of these differences, these in vitro studies provide insight into the possible use of
B. trimera for treating obesity.

14
Corroborating these findings, the treatment of obese rats from a high-fat diet
with the methanol extract of the bark of B. trimera reduced body weight and serum
cholesterol levels. In this study, animals were treated for 35 days with doses of 2
mg/day or 100 mg/day (to mimic doses of 1 g/70 kg/day and 50 g/ 70 kg/day,
respectively) concomitantly with the high-fat diet and similar effects were observed
with both groups (de Souza et al., 2012).

This evidence indicates that methanol extract of B. trimera can be promising to


treat obesity and/or reduce body weight; however, more in vivo and in vitro studies are
required to further evaluate its potential. Future studies may also include toxicological
parameters because there is still little information on the toxic potential of B. trimera.

In this context, it is worthwhile to mention that Nogueira et al. (2011) described


genotoxicity but not mutagenicity in mice by administering 42 mg/kg of aqueous extract
of B. trimera, as well as the toxicological effects on kidney cells in vitro. Conversely,
another study showed that female adult mice treated with 500, 1,000 or 2,000 mg/kg of
aqueous extract of B. trimera presented no genotoxic effect in the liver and showed an
antigenotoxic effect in the blood, providing protection to cells against oxidative DNA
damage (Rodrigues et al., 2009). Furthermore, Grance et al. (2008) observed that the
administration of 8.4 mg/kg of the hydroethanol extract of B. trimera to pregnant rats
was toxic to maternal kidney and liver cells. Altogether, these data indicate that care
should be taken when using this plant.
Some of the main bioactive compounds obtained from ethanol or water extracts
of B. trimera are saponins, mainly echinocystic acid, and the flavonoids rutin (Gene et
al., 1996), apigenin, quercetin, luteolin, eupafolin, and hispidulin (Soicke and Leng-
Peschlow, 1987).
Among these compounds, some were investigated in studies in vitro or animal
models related to obesity. For example, the administration of rutin as a supplement (50
mg/kg for 8 weeks) decreased body weight, the mass of the peritoneal and epididymal
adipose fat pads, serum lipids, hepatic triglycerides, cholesterol and oxidative stress in
rats treated with a high-fat diet (Hsu et al., 2009).
Moreover, the incubation of apigenin with rat 3T3-L1 cells suppressed adipocyte
differentiation and reduced the accumulation of intracellular lipids, possibly due to the
apigenin-induced activation of 5'-adenosine monophosphate-activated protein kinase

15
and decreased expression of adipogenic and lipolytic genes, thus suppressing
adipogenesis (Ono and Fujimori, 2011).
Hil et al. (2015) showed that supplementation of diet with apigenin or quercetin
(0.01 mol/kg of diet each) reduced the body weight of high-fat diet-fed mice. These
authors also observed that hepatic lipid accumulation, mesenteric adipose tissue weight
and serum leptin levels were significantly lowered by quercetin. In accordance with
these findings, in their review, Nabavi and coworkers (2015) proposed that mitogen-
activated protein kinase and adenine monophosphate-activated protein kinase signaling
pathways are mechanisms involved in the anti-obesity effect of quercetin.
Luteolin was also described as a flavonoid with potential anti-obesity properties.
Xu et al. (2014) showed that luteolin suppressed body weight gain, fat deposition and
adipocyte hypertrophy and partially reversed glucose intolerance and insulin sensitivity
in mice fed a high-fat diet. Kwon et al. (2015) observed that luteolin reduced the
expression of genes controlling adiposity and increased PPAR-γ protein expression in
adipose tissue, which led to the improvement in circulating fatty acid levels and was
linked to improved hepatic steatosis in mice fed a high-fat diet for 16 weeks.
Taken together, these studies emphasize the possibility that B. trimera possesses
anti-obesity properties and strongly reinforces the need for more studies to investigate
this potential, along with toxicological studies and the chemical determination of the
percentages of these compounds in B. trimera.

3.2. Annona muricata L.


Annona muricata L. (Annonaceae), popularly known as “graviola,” is found in
tropical and subtropical parts of the world, mainly Central and South America but also
India, Malaysia and Nigeria (Moghadamtousi et al., 2014). In Brazil, studies on the
traditional use of A. muricata were conducted in the states of Rondônia, Ceará,
Pernambuco, Bahia and Minas Gerais. It is widely used for body weight loss, treatment
of infections, snake bites, cancer, dyspnea, hypertension, diabetes, fever, inflammation,
low back pain and dizziness (dos Santos and de Lima, 2008; Grandi et al., 1989;
Liporacci and Simão, 2013; Macêdo et al., 2013; Moreira et al., 2002; Santos et al.,
2012).
Experimental studies have shown many activities for preparations of parts of A.
muricata. Treatment with ethanol extract from the stem bark of A. muricata (200
mg/kg, daily, for 28 days) showed protective effects against oxidative stress and

16
alteration of hepatic enzymes induced by carbon tetrachloride in rats (Olakunle et al.,
2014). In addition, a gastroprotective effect was described by treatment with ethyl
acetate extract from the leaves of A. muricata (Moghadamtousi et al., 2014). Moreover,
the anti-inflammatory and antinociceptive activities of ethanol extract of the leaves of A.
muricata were observed in rodents (Roslida et al., 2010; de Sousa et al., 2010).
In spite of the description of the use of infusion or decoction of the leaves of A.
muricata by people to lose weight (dos Santos and de Lima, 2008; Grandi et al., 1989;
Liporacci and Simão, 2013; Macêdo et al., 2013; Moreira et al., 2002; Santos et al.,
2012), there is no published scientific evidence to support this use either in vitro or in
laboratory animals.
Using the model of alloxan-induced diabetic rats, Ahalya et al. (2014) showed
that the ethanol extract of the stem bark of A. muricata caused antidiabetic and
hypolipidemic effects. The treatment of rats with this extract (150 or 300 mg/kg) for 14
days lowered the blood glucose and reduced cholesterol and triglyceride levels (Ahalya
et al., 2014), which are characteristics found both in obese experimental animals and
people.
A variety of compounds have been identified in many parts of A. muricata and
have been reviewed by Moghadamtousi et al. (2014). In the leaves of this plant, a
variety of annonaceous acetogenins were found, but the biological activities of these
compounds are more related to cytotoxicity against tumoral cell lines (Wu et al., 1995a,
b; Zeng et al., 1996). In addition, in the leaves of A. muricata, some alkaloids
(reticuline, coreximine, coclaurine, atherosperminine, stepharine) (Leboeuf et al., 1981)
and essential oils (β-caryophyllene, δ-cadinene, epi-α-cadinol and α-cadinol) were
identified (Kossouoh et al., 2007). Many flavonol triglycosides, such as quercetin 3-O-
α-rhamnosyl-(1→6)-β-sophoroside, gallic acid, epicatechin, kaempferol 3-O-rutinoside,
quercetin 3-O-glucoside, quercetin and kaempferol were found in the aqueous extract of
leaves of this plant (Nawwar et al., 2012). Of interest, kaempferol affected adipocyte
differentiation in 3T3-L1 cells and zebrafish, resulting in anti-adipogenic effects (Lee et
al., 2015). In addition, Zang and coworkers (2015) demonstrated that high-fat-fed mice
treated with 0.15% dietary kaempferol glycosides for 92 days presented a reduction of
body weight, the accumulation of adipose tissue, fasting blood glucose, insulin
resistance, hyperlipidemia and hyperglycemia. Additionally, the above-mentioned
studies (Hil et al., 2015; Nabavi et al., 2015) have highlighted the effect of quercetin
(also found in A. muricata) on obesity in experimental animals.

17
In this way, although no study has related preparations from the leaves of A.
muricata with anti-obesity effects, there are many indications that this plant contains
chemical compounds that can induce such activity. It remains unclear whether these
compounds are present in A. muricata leaves in amounts sufficient to produce any anti-
obesity effects, as well as whether some synergistic action could take place to benefit
the treatment of obesity. Further studies may contribute to the understanding the
potential of this plant to cause weight loss and treat obesity.
Toxicological evaluation of A. muricata is necessary to establish the safety of
this plant. Awodele et al. (2014) administered A. muricata fruit juice (80, 400 and 2,000
mg/kg) to rats to investigate acute and 60-day subchronic toxicity. They found no
significant changes in the weight of vital organs and hematological and biochemical
parameters. However, some studies have associated the excessive consumption of
annonaceous acetogenins to a potential risk for neurotoxic effects (Bonneau et al. 2012;
see Moghadamtousi et al., 2015 for revision). This might be of importance because
annonaceous acetogenins are also found in the leaves of A. muricata.

3.3. Hancornia speciosa Gomes


Hancornia speciosa Gomes (Apocynaceae) produces an edible fruit and is an
important rubber-producing plant found in Brazilian Cerrado (Soares et al., 2007). The
pulp and the peel of the fruit are consumed in natura in ice creams, jellies, candies and
liqueurs, and the latex is used for rubber production (da Rosa et al., 2007).
In an ethnobotanical survey, Santos et al. (2013) verified the use of this species
for the treatment of diabetes, tuberculosis, lower back pain, hypertension, menstrual
cramps, respiratory and venereal diseases, dislocation, dermatosis and ulcers, in
addition to obesity. Anti-obesity was cited in four studies on the popular use of this
plant, and the most common use was the decoction of the inner bark (da Silva et al.,
2010; Grandi et al., 1989; Santos et al., 2013; Silva et al., 2010). It was one of the most
cited plants in Nova Xavantina (Mato Grosso State) and in many cities of Minas Gerais
State (Grandi et al., 1989; Silva et al., 2010). In this way, this plant seems to be a good
candidate for future research focused on treating obesity.
In spite of the popularity of the inner bark of H. speciosa for treating obesity, we
found no study in the literature that validated this use. However, pharmacological
studies have provided data on the other actions of H. speciosa. Treatment with the
hydroalcohol extract of the bark of H. speciosa (500 mg/kg) reduced the gastric ulcer,

18
probably due the antioxidant properties of polymeric proanthocyanidins (Moraes et al.,
2008). Interestingly, in this study, authors observed absence of toxicity following
administration of 5 g/kg of this extract to mice. Additionally, the ethanol extract of the
leaves of H. speciosa induced endothelium-dependent vasodilation of rat aortic rings,
through activation of phosphatidylinositol 3-kinase (Ferreira et al., 2007) or induced
hypotension in rats due to inhibition of angiotensin-converting enzyme and increase of
nitric oxide (Silva et al., 2011). In addition, Marinho et al. (2011) demonstrated the anti-
inflammatory effects of the latex of the tree trunk of H. speciosa (0.06-1.3 mg/kg) in
rodents via the inhibition of prostaglandin E2 and the production of cytokines.
More recently, Pereira et al. (2015) showed that ethanol extract of the leaves of
H. speciosa and its dichloromethane fraction inhibited α-glucosidase in vitro and
increased glucose uptake in freshly dissociated adipocytes. In addition, they
demonstrated reduced glycemia in both starch and glucose tolerance tests in mice at the
dose of 300 mg/kg of this extract or its dichloromethane fraction. It is interesting that
while ethnobotanical studies described the popular use of H. speciosa for weight loss to
be mainly related to preparations of the bark, the evidence provided by Pereira et al.
(2015) showed that the leaves of this plant may also present some potential to induce
such activity.
According to Silva et al. (2010), the leaves and bark of H. speciosa contain
alkaloids, flavonoids and tannins. Endringer et al. (2009) described that the ethanol
extract of the leaves contains rutin, bornesitol and quinic acid, and these compounds
caused nuclear factor-kB inhibition in cells stimulated in vitro. Pereira et al. (2015) also
showed that bornesitol and quinic acid were found in the ethanol extract of the leaves,
along with chlorogenic acid (an ester of caffeic acid and quinic acid) and flavonoid
glycosides. Simultaneously, they found esters of lupeol and/or α/β-amirin in the
dichloromethane fraction of this extract. In addition to rutin (Hsu et al., 2009; Panchal et
al., 2011), chlorogenic acid and quinic acid were also described as polyphenol
compounds that reduce obesity effects in experimental animals. For instance, the
supplementation of water (0.21 mg/mouse/day) with chlorogenic acid and its isomers
(3-O-caffeoylquinic acid [3-CQA], 4-CQA and 5-CQ) plus 0.1 mg/mouse/day of
caffeine for 4 weeks reduced insulin resistance, glucose tolerance and body weight in
mice fed a high-fat diet (Ghadieh et al., 2015).
In this way, although no study has assured the weight reduction effect of H.
speciosa on human or experimental animals, research with polyphenols found that parts

19
of this plant (especially leaves) have demonstrated a potential for obesity treatment in
animals. This is in contrast with the popular use of the decoction or infusion of barks of
this plant, which was found in the present review. It is also important to mention that
there is no study on the possible toxic effects of this plant.

3.4. Other species


Other species cited in a considerable amount of studies can be highlighted:
Camellia sinensis (L.) Kuntze, Cynara scolymus L., Achyrocline satureioides (Lam.)
DC. and Rudgea virburnoides (Cham.) Benth.
Camellia sinensis (L.) Kuntze, popularly known as green tea, possesses
catechins, such as epigallocatechin-3-gallate, as well as quercetin, thearubigins,
theaflavins, theanine, caffeine, chlorogenic acid and gallic acid (Astell et al., 2013). The
effect of green tea on obesity and body weight loss is extensively described and
discussed in nutritional research (Grove and Lambert, 2010; Huang et al., 2014).
According to the recent review by Huang et al. (2014), no optimal dose has been
established due to the diversity of variables involved in the studies, such as the
participants’ lifestyles and metabolic risk factors. However, these authors argued that
green tea can reduce food intake, lipid absorption and adipogenesis, as well as improve
energy expenditure via thermogenesis, fat oxidation and fecal lipid excretion. Moreover,
caution should be taken when using green tea, especially in high doses because it seems
to be correlated to hepatotoxicity (Huang et al., 2014; Mazzanti et al., 2009).
Cynara scolymus L., popularly known as the artichoke, has presented promising
activity. A purified extract of its flowers (500–1,500 mg/kg) elicited a reduction of post-
prandial glycemia in both Wistar and genetically obese Zucker rats treated acutely
(Fantini et al., 2011). Treatment with artichoke leaf extract (1,500 mg/kg) decreased
serum triglycerides and cholesterol levels in rats given a high cholesterol diet (Kusku-
Kiraz et al., 2010). Interestingly, treatment with leaf extract (250 mg, twice a day)
decreased the total cholesterol and LDL levels and increased HDL levels in humans
with hypercholesterolemia (Rondanelli et al., 2013). Additionally, a high molecular
weight inulin isolated from this plant had a prebiotic effect (Lopez-Molina et al., 2005).
Popularly known as “macela,” Achyrocline satureioides (Lam.) DC. contains
quercetin and luteolin as bioactive compounds. The anti-inflammatory activity of the
aqueous or ethanol extracts was described in mice (Simoes et al., 1988), as well as its
antioxidant activity and inhibitory effect on both human blood-derived LDL oxidation

20
induced by copper, lipoxygenase or peroxynitrite and the aggregation of apolipoprotein
B induced by copper (Gugliucci and Menini, 2002). However, no experimental study
has related this plant to obesity.
One study regarding to the effect of Rudgea virburnoides (Cham.) Benth.,
known as “congonha-de-bagre,” showed favorable effects. Rats treated only with the
aqueous extract of the leaves of this plant (daily dose of 10 or 20 g of dry leaves/L of
water) reduced plasma triglyceride concentrations, but increased deposits of fat in the
liver (Monteiro et al., 2009).
Among species with only one citation, some can be highlighted: Allium sativum
L., Anacardium occidentale L., Annona montana Macfad., Asparagus officinalis L.,
Campomanesia xanthocarpa (Mart.) O.Berg, Cinnamomum verum J.Presl, Citrus limon
(L.) Osbeck, Cymbopogon citratus (DC.) Stapf, Guazuma ulmifolia Lam., Hibiscus
sabdariffa L., Mimosa pudica L. and Stevia rebaudiana (Bertoni) Bertoni.
Largely used as a condiment, Allium sativum L., or garlic, is widely known and
used by the general population. Macêdo et al. (2013) stated that people use garlic in
Ceará State (Brazil) as a decoction or infusion or even lick it to produce weight loss.
Some scientific evidence corroborates this use. In rats fed a high-fat diet for 12 weeks,
the administration of garlic extract (250 or 500 mg/kg/day) for 28 days reduced plasma
insulin, total cholesterol and oxidative stress, as it restored the variability of the heart
rate, cardiac function and cardiac mitochondrial function that were compromised by the
consumption of the high-fat diet (Supakul et al., 2014). In mice made obese by a high-
fat diet, the administration of garlic stem extract at doses of 100, 250 and 500 mg/kg
inhibited body weight gain, adipose tissue weight, adiponectin and leptin levels, serum
and hepatic lipid parameters and liver fat accumulation and oxidative stress (Kim et al.,
2013). Some compounds isolated from garlic were also tested in adipocytes in vitro. A
garlic-derived organosulfur, 1,2-vinyldithiin, reduced the expression of the proliferator
peroxisome-activated receptor gamma 2, lipoprotein lipase, leptin and adiponectin
genes in human preadipocytes, culminating in reductions in lipid accumulation and the
inhibition of interleukin-6 and monocyte chemoattractant protein-1 induced by
macrophage-secreted factors (Keophiphath et al., 2009). Thiacremonone, a sulfur
compound isolated from garlic, inhibited 3T3-L1 adipocyte differentiation by a decrease
in transcription factors related to adipogenesis, without causing a cytotoxic effect in
these cells (Kim et al., 2012). Alliin (a S-allyl cysteine sulfoxide) caused a reduction in
the interleukin-6 and mRNA expression of monocyte chemoattractant protein-1, as well

21
as the phosphorylation of ERK1/2 in 3T3-L1 adipocytes exposed to LPS (Quintero et
al., 2013). Altogether, these results corroborate the popular use of garlic described by
Macêdo et al. (2013), but the demonstration of weight loss or anti-obesity properties in
humans it is still a matter of interest.
Studies with Hibiscus sabdariffa L. ("hibiscus") have shown substantial effects
on obesity. Alarcon et al. (2007) observed a less pronounced body weight gain in obese
mice treated with aqueous extract of the flowers (120 mg/kg) of this plant. Additionally,
Chang et al. (2014) showed that aqueous extract of the flowers of hibiscus reduced body
weight, total body fat, liver fat and waist-hip ratio in humans. Many polyphenols were
detected in sun-dried calyces of H. sabdariffa, but their beneficial effect on 3T3-L1
adipocytes seemed to be greater for the whole extract than the sum of its parts (Herranz
et al., 2012). Furthermore, this study showed that the aqueous extract of this plant had a
greater inhibitory effect on triglyceride accumulation, reactive oxygen species
generation and adipokine secretion when devoid of fiber and polysaccharides. Aqueous
extract of H. sabdariffa is also considered to be safe at doses of 300 mg/kg/day in
human and animal studies (see Hopkins et al., 2013 for review) and hepatotoxic at very
high doses in rats (2 g/kg/day, over 90 days; Fakeye et al., 2009).
The aqueous extract of leaves (175 mg/kg) of Anacardium occidentale L. or
“cajueiro” was shown to impair the increase in glucose levels, polydipsia and polyphagy
in streptozotocin-induced diabetes in rats (Kamtchouing et al., 1998). In addition, the
supplementation of a casein diet of rats with cashew globulins of A. occidentale
decreased lipid metabolism, leading to the reduction of serum and tissue (heart, adipose
and liver) lipids (Prabha and Rajamohan, 1998).
Annona montana Macfad. is also called “jaca-de-pobre” or “falsa graviola” and
is rich in acetogenins (Mootoo et al., 2000). In a study conducted by Barbalho et al.
(2012), the pulp juice reduced body weight and serum glucose and lipids as well as
increased serum HDL in naive rats.
Asparagus officinalis L. or “aspargo” also reduced body weight in humans (in a
supplement with Sambucus nigra; Chrubasik et al., 2008) and blood glycemia and
triglyceride levels in streptozotocin-induced diabetes in rats (aqueous extract of the
plant; Zhao et al., 2011) and total cholesterol and LDL in rats fed a diet rich in
cholesterol (administration of freeze-dried aspargo; Garcia et al., 2012).
Aqueous extracts from Campomanesia xanthocarpa (Mart.) O.Berg
(“guabiroba”) reduced body weight and blood glucose concentrations in rats fed with a

22
high-calorie diet when compared to normal diet-treated rats (Biavatti et al., 2004).
Interestingly, Viecili et al. (2014) reported that administration of capsules containing
dried leaves of C. xanthocarpa (500 – 1,000 mg) reduced triglycerides and LDL-
cholesterol concentrations in hypercholesterolemic individuals.
Cinnamomum verum J.Presl or “canela-da-índia” is rich in polyphenols (Im et
al., 2014). Ranasinghe et al. (2012) revised the efficacy and safety of this plant to treat
diabetes and indicated that it improved glycemia due to the postprandial absorption of
glucose, increased the translocation of GLUT-4, inhibited gluconeogenesis, stimulated
insulin release, and increased the HDL concentration in blood. In addition, Shatwan et
al. (2013) demonstrated that treatment with crude C. zeylanicum (C. verum synonym)
reduced serum lipid and leptin and increased adiponectin levels in diabetic rats.
Studies with the lyophilized juice of Citrus limon (L.) Osbeck (5 g/kg) or an
aqueous extract of the fresh leaves of Cymbopogon citratus (DC.) Stapf (“capim
cidreira”; 125-500 mg/kg) reduced serum cholesterol and triglyceride levels (Adeneye
and Agbaje, 2007; Trovato et al., 1996). Additionally, Adeneye and Agbje (2007)
showed that the above-mentioned preparation of C. citratus decreased glucose levels of
normoglycemic rats.
An interesting effect was shown for Guazuma ulmifolia Lam., popularly known
as “chico-magro.” Alonso and Salazar (2008) demonstrated that the aqueous extract of
the bark of this plant altered the uptake of glucose, improving glucose homeostasis, both
in insulin-sensible and insulin-resistant 3T-F442A adipocytes, without interfering with
adipogenesis.
The chloroform extract of the leaves of Mimosa pudica L. (“dorme-dorme”)
(200 mg/kg) showed a reducing effect on serum lipids, total cholesterol, LDL, VLDL,
and triglycerides and an increase in serum HDL levels in rats (Rajendran and
Krishnakumar, 2010).
Stevia rebaudiana (Bertoni) Bertoni, also known as stevia, is an alternative
source of natural sugar. In mice fed a high-fat diet, treatment with sucrose from S.
rebaudiana (stem and leaves) suppressed body weight gain, reduced serum cholesterol
and triglyceride levels and liver fat, as well as increased the concentration of free
carnitine (Park and Cha, 2010). Kujur et al. (2010) observed the reduction of glycemia
in diabetic rats treated with the extract of the leaves (2 g/kg) of stevia. However, no
effect was observed by Oliveira-Filho et al. (1989) on glycemia, body weight, thyroxine

23
(T4) and triiodothyronine (T3) concentrations or other endocrine parameters in rats
chronically treated with the aqueous extracts of the leaves of S. rebaudiana.
Concerning the other species identified in the present study, although they were
cited in ethnobotanical studies to be useful for the treatment of obesity and overweight,
it was not verified scientifically whether they were effective in the treatment of obesity
or other conditions such as hyperglycemia or dyslipidemias. The activities found for
these plants referred to the effect on hypertension (Scutia buxifolia Reissek; da Silva et
al., 2012), nociception (Vernonia condensata Baker and Solanum cernuum Vell.; da
Silva et al., 2013; Frutuoso et al., 1994; Lopes et al., 2014), inflammation (V.
condensata, Echinodorus macrophyllus (Kunth) Micheli, Symphytum officinale L., S.
cernuum; Araujo et al., 2012; da Silva et al., 2011; Lopes et al., 2014; Tanus et al.,
2010), gastric ulcer (V. condensata; Frutuoso et al., 1994), kidney damage (E.
macrophyllus; Nascimento et al., 2014), wound repair (S. officinale; Araujo et al.,
2012), microbial infection and cancer (Senna occidentalis (L.) Link; Lombardo et al.,
2009).

24
4. Concluding remarks
The present review shows that many plants are used by the population for weight
loss or as anti-obesity agents, but few plants have had their usage scientifically
corroborated. Among these plants, the strongest evidence for anti-obesity action was
observed for C. sinensis and H. sabdariffa, although the safety of these plants is still a
matter of interest. Other species cited by the population were tested in animal models of
obesity, such as B. trimera, A. sativum, A. officinalis, C. xanthocarpa or S. rebaudiana,
and the scientific evidence suggests potential for the treatment of obesity that remains to
be investigated.
Although there is a complete lack of scientific evidence that validates the
potential of the other species highlighted in this review, many of them have shown
relevant effects on glycemia, serum lipids and/or body weight in experimental animals,
which are factors that do not directly correspond to obesity or overweight but are
usually altered in these conditions.
It is also worthwhile to observe that the majority of studies that investigated the
effects of the species emphasized in the present review were performed in animal
models. Thus, studies that assure the anti-obesity effect, the underlying mechanisms of
action, long-term safety and potential toxicological effects are clearly necessary to
clarify their appropriate use in humans.
In conclusion, little scientific evidence was found in the literature to corroborate
the traditional use of the majority of plants in Brazil for weight loss or the treatment of
obesity. Considering the small number of studies and the lack of scientific basis, more
pharmacological investigations in vivo or in vitro would be of value for these plants.
The present review can guide researchers on their choice of the plants for future
scientifically controlled studies based on the ethnobotanical data. This could confirm
their use by the population and permit new alternatives based on phytotherapy to treat
obese and overweight people. Moreover, these studies should report not only the
magnitude of the effects, but also the potential side effects and long-term safety.

Acknowledgments:
We thank the “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior”
(CAPES; Social Demand Program of Scholarships) and Conselho Nacional de Pesquisa
e Desenvolvimento Científico (CNPq) for financial support. EAC and MRVS are
beneficiaries of CNPq productivity grants.

25
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